Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial

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• 作者：Dr Rafael Rosell ; MD^a ; ^b ; ^{rrosell@iconcologia.net} ; Enric Carcereny ; MD^a ; Radj Gervais ; MD^c ; Prof Alain Vergnenegre ; MD^d ; Bartomeu Massuti ; MD^e ; Enriqueta Felip ; MD^f ; Ramon Palmero ; MD^g ; Ramon Garcia-Gomez ; MD^h ; Cinta Pallares ; MDⁱ ; Jose Miguel Sanchez ; MD^j ; ^k ; Rut Porta ; MD^l ; Manuel Cobo ; MD^m ; Pilar Garrido ; MDⁿ ; Flavia Longo ; MD^o ; Teresa Moran ; MD^a ; Amelia Insa ; MD^p ; Filippo De Marinis ; MD^q ; Romain Corre ; MD^r ; Isabel Bover ; MD^s ; Alfonso Illiano ; MD^t ; Eric Dansin ; MD^u ; Javier de Castro ; MD^v ; Michele Milella ; MD^w ; Noemi Reguart ; MD^x ; Giuseppe Altavilla ; MD^y ; Ulpiano Jimenez ; MD^z ; Mariano Provencio ; MD^aa ; Miguel Angel Moreno ; MD^ab ; Josefa Terrasa ; MD^ac ; Jose Muñ ; oz-Langa ; MD^ad ; Javier Valdivia ; MD^ae ; Dolores Isla ; MD^af ; Manuel Domine ; MD^ag ; Olivier Molinier ; MD^ah ; Prof Julien Mazieres ; MD^ai ; Nathalie Baize ; MD^aj ; Rosario Garcia-Campelo ; MD^ak ; Gilles Robinet ; MD^al ; Delvys Rodriguez-Abreu ; MD^am ; Guillermo Lopez-Vivanco ; MD^an ; Vittorio Gebbia ; MD^ao ; Lioba Ferrera-Delgado ; MD^ap ; Pierre Bombaron ; MD^aq ; Reyes Bernabe ; MD^ar ; Alessandra Bearz ; MD^as ; Angel Artal ; MD^at ; Enrico Cortesi ; MD^au ; Christian Rolfo ; MD^av ; Maria Sanchez-Ronco ; PhD^aw ; Ana Drozdowskyj ; PhD^ax ; Cristina Queralt ; PhD^a ; Itziar de Aguirre ; PhD^a ; Jose Luis Ramirez ; PhD^a ; Prof Jose Javier Sanchez ; MD^ay ; Miguel Angel Molina ; PhD^b ; Miquel Taron ; PhD^a ; ^b ; Luis Paz-Ares ; MD^az ; on behalf of the Spanish Lung Cancer Group in collaboration with the Groupe Franç ; ais de Pneumo-Canc&eacute ; rologie ; the Associazione Italiana Oncologia Toracica
• 刊名：Lancet Oncology
• 出版年：2012
• 出版时间：March, 2012
• 年：2012
• 卷：13
• 期：3
• 页码：239-246
• 全文大小：246 K

文摘

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Summary

Background

Erlotinib has been shown to improve progression-free survival compared with chemotherapy when given as first-line treatment for Asian patients with non-small-cell lung cancer (NSCLC) with activating EGFR mutations. We aimed to assess the safety and efficacy of erlotinib compared with standard chemotherapy for first-line treatment of European patients with advanced EGFR-mutation positive NSCLC.

Methods

We undertook the open-label, randomised phase 3 EURTAC trial at 42 hospitals in France, Italy, and Spain. Eligible participants were adults (>18 years) with NSCLC and EGFR mutations (exon 19 deletion or L858R mutation in exon 21) with no history of chemotherapy for metastatic disease (neoadjuvant or adjuvant chemotherapy ending ? months before study entry was allowed). We randomly allocated participants (1:1) according to a computer-generated allocation schedule to receive oral erlotinib 150 mg per day or 3 week cycles of standard intravenous chemotherapy of cisplatin 75 mg/m² on day 1 plus docetaxel (75 mg/m² on day 1) or gemcitabine (1250 mg/m² on days 1 and 8). Carboplatin (AUC 6 with docetaxel 75 mg/m² or AUC 5 with gemcitabine 1000 mg/m²) was allowed in patients unable to have cisplatin. Patients were stratified by EGFR mutation type and Eastern Cooperative Oncology Group performance status (0 vs 1 vs 2). The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. We assessed safety in all patients who received study drug (? dose). This study is registered with , number .

Findings

Between Feb 15, 2007, and Jan 4, 2011, 174 patients with EGFR mutations were enrolled. One patient received treatment before randomisation and was thus withdrawn from the study; of the remaining patients, 86 were randomly assigned to receive erlotinib and 87 to receive standard chemotherapy. The preplanned interim analysis showed that the study met its primary endpoint; enrolment was halted, and full evaluation of the results was recommended. At data cutoff (Jan 26, 2011), median PFS was 9¡¤7 months (95 % CI 8¡¤4-12¡¤3) in the erlotinib group, compared with 5¡¤2 months (4¡¤5-5¡¤8) in the standard chemotherapy group (hazard ratio 0¡¤37, 95 % CI 0¡¤25-0¡¤54; p<0¡¤0001). Main grade 3 or 4 toxicities were rash (11 [13 % ] of 84 patients given erlotinib vs none of 82 patients in the chemotherapy group), neutropenia (none vs 18 [22 % ]), anaemia (one [1 % ] vs three [4 % ]), and increased amino-transferase concentrations (two [2 % ] vs 0). Five (6 % ) patients on erlotinib had treatment-related severe adverse events compared with 16 patients (20 % ) on chemotherapy. One patient in the erlotinib group and two in the standard chemotherapy group died from treatment-related causes.

Interpretation

Our findings strengthen the rationale for routine baseline tissue-based assessment of EGFR mutations in patients with NSCLC and for treatment of mutation-positive patients with EGFR tyrosine-kinase inhibitors.

Funding

Spanish Lung Cancer Group, Roche Farma, Hoffmann-La Roche, and Red Tem¨¢tica de Investigacion Cooperativa en Cancer.